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Related Concept Videos

Insertion of Single-pass Transmembrane Proteins in the RER01:26

Insertion of Single-pass Transmembrane Proteins in the RER

Integral membrane proteins are proteins adhered to the lipid bilayer of a cell organelle or membrane. They can be of two types: transmembrane integral proteins that span the lipid bilayer and monotopic proteins that are attached to either side of the membrane but do not pass through it.
Integral transmembrane proteins possess transmembrane and extra membrane domains. The transmembrane domains are primarily made of 20-25 hydrophobic amino acids arranged in a helical secondary confirmation. These...
Protein Transport into the Inner Mitochondrial Membrane01:34

Protein Transport into the Inner Mitochondrial Membrane

Nuclear encoded mitochondrial precursors are imported to the inner membrane in a multistep process involving two separate translocons, TIM22 and TIM23. TIM23 is a cation-selective pore that remains closed by the N terminal segment of the protein. Negative charges on the TIM23 act as a receptor for the incoming precursor, pulling the positively charged matrix-targeting sequence for peptide insertion and translocation.
Transport of mitochondrial precursors across the TIM23 channel is driven by...
Porin Insertion in the Outer Mitochondrial Membrane01:12

Porin Insertion in the Outer Mitochondrial Membrane

Porins are beta-barrel proteins translocated to the mitochondrial outer membrane through the TOM complex into the intermembrane space. Porin precursors bind TIM chaperones within the intermembrane space and are guided to the Sorting and Assembly Machinery complex or SAM complex on the outer mitochondrial membrane.
Three models describe the assembly of porins by the SAM complex and their insertion into the outer membrane. Model 1 suggests that porins are assembled outside the SAM channel as the...
Multi-pass Transmembrane Proteins and β-barrels01:09

Multi-pass Transmembrane Proteins and β-barrels

In multi-pass transmembrane proteins, the polypeptide chain crosses the membrane more than once. The transmembrane polypeptide chain either forms an α-helix or β-strand structure. α-Helix containing multi-pass transmembrane proteins are ubiquitous, whereas β-strand containing ones are mainly found in gram-negative bacteria, mitochondria, and chloroplasts.
α-Helix containing multi-pass transmembrane proteins
Multi-pass transmembrane proteins such as G-protein-linked receptors (GPCRs) and...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...
Voltage-gated Ion Channels01:26

Voltage-gated Ion Channels

Voltage-gated ion channels are transmembrane proteins that open and close in response to changes in the membrane potential. They are present on the membranes of all electrically excitable cells such as neurons, heart, and muscle cells.
Generally, all voltage-gated ion channels have a 'voltage-sensing domain' that spans the lipid bilayer. The charged residues in the sensor move in response to the membrane potential changes that open the channel allowing ions movement. There are several types of...

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Functional Site-Directed Fluorometry in Native Cells to Study Skeletal Muscle Excitability
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Membrane insertion of a voltage sensor helix.

Chze Ling Wee1, Alan Chetwynd, Mark S P Sansom

  • 1Department of Biochemistry, University of Oxford, United Kingdom.

Biophysical Journal
|January 20, 2011
PubMed
Summary

The S4 helix, crucial for voltage sensor domains, can stably insert into lipid bilayers. This occurs because its hydrophobic residues favor membrane insertion more than charged residues penalize it.

Area of Science:

  • Biophysics
  • Molecular Biology
  • Membrane Protein Structure

Background:

  • Transmembrane (TM) helices are common in membrane proteins, typically hydrophobic.
  • The S4 helix in voltage sensor (VS) domains is unique, containing charged residues yet spanning the membrane.
  • Understanding S4 helix insertion is key to translocon-mediated protein insertion mechanisms.

Purpose of the Study:

  • To investigate the stabilization mechanisms of a charged TM S4 alpha-helix within a lipid bilayer.
  • To explore the thermodynamic favorability of S4 helix insertion into membranes.
  • To elucidate the physical basis for the stable TM orientation of the S4 helix.

Main Methods:

  • Multiscale molecular dynamics simulations.
  • Free-energy profile calculations for helix insertion into phospholipid bilayers.

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  • Analysis of residue interactions and bilayer properties.

    • Main Results:

    • Insertion of the S4 helix from water to the membrane center is thermodynamically favorable.
    • The S4 helix adopts a stable TM orientation within the lipid bilayer.
    • Hydrophobic residue preference for bilayer insertion overcomes the penalty of charged residues, enabling stable insertion.

    Conclusions:

    • The S4 helix's unique charge and hydrophobic composition facilitates stable membrane insertion.
    • Simulation results align with experimental data from Kv channels and VS domains.
    • This study provides insights into the biophysical principles governing charged helix insertion into membranes.